The subject matter disclosed herein relates generally to pharmaceutical dosage forms comprising a drug. The pharmaceutical dosage forms generally relate to immediate release, controlled release, and/or combinations of both immediate and controlled release dosage forms. The subject matter additionally relates to formulations containing said controlled release beads, and to methods of preparing said beads. The subject matter further relates to stabilized tolterodine tartrate formulations.
Controlled release dosage forms, may include particles or beads containing a drug or active agent, where the particles or beads are coated with a release-controlling polymer. Controlled release beads may comprise an inert core, coated with an inner drug-containing layer and an outer membrane layer controlling drug release from the inner layer. The inert core may be a sphere or bead of sugar, a hydrophilic cellulosic polymer, or a crosslinked hydrophilic synthetic polymer.
Examples of controlled release beads may comprise a core unit of an inert material; an active ingredient-containing layer on the core unit, which may also contain a hydrophilic polymer; and a polymeric outer membrane layer effective for controlled release of the active ingredient. The membrane modifying and controlling the drug release can be a pH-dependent enteric coating, or a pH-independent permeable coating. Either the enteric coatings or the pH-independent permeable coatings may be used in combination with a water-soluble polymer or non-polymer as a pore forming agent to adjust the permeability of the coating layer.
In some controlled release beads interaction between the core layer and the active-ingredient containing layer may lead to drug degradation. For example, solid oral dosage forms containing water-soluble drugs, such as tolterodine tartrate, can undergo a slow topochemical degradation, leading to a reduction in the purity of the active ingredient and in the potency of the dosage form. Such solid oral dosage forms include tablets and solid-filled capsules.
Tolterodine tartrate is a muscarinic receptor antagonist that is used to treat urinary incontinence. Tolterodine acts on M2 and M3 subtypes of muscarinic receptors whereas most antimuscarinic treatments for overactive bladder only act on M3 receptors making them more selective. Tolterodine, although it acts on two types of receptors, has fewer side effects than other antimuscarinics, such as oxybutynin (which is selective for M3 receptors only) as tolterodine targets the bladder more than other areas of the body. This means that less active agents need to be given daily (due to efficient targeting of the bladder) and so there are fewer side effects. Common side effects of tolterodine tartrate include hyposalivation, constipation, and decreased gastric motility.